The mechanism by which heterologous anti-lymphocyte globulin suppresses the immune response to allotransplantation is not clearly understood. It is the purpose of this project to characterize the specific nature of the immunological suppression incurred by the administration of rabbit anti-human thymocyte globulin of high immunosuppressive capability. Specifically, we are interested in demonstrating whether antibody with specificity to thymus derived lymphocytes (T cells) is present in our preparations of RATG and the extent to which this moiety is responsible for the potent immunosuppressive effect of RATG on allotransplantation immunity. Crude rabbit anti-human thymocyte globulin (RATG) and absorbed T cell specific RATG preparations will be compared in the surrogate primate model for their activity in suppressing allograft rejection, for their titers obtained in lymphocytotoxicity, mixed agglutination, and T cell rosette inhibition assays with human and primate lymphocyte target cells, and for their effect in vivo and in vitro on the suppression of non-specific mitogen induced blast transformation, specific blast transformation in the mixed lymphocyte culture (MLC) reaction, and on cytotoxic effector cell function in the cell mediated lympholysis assay (CML). The degree of activity of RATG preparations in in vitro assays will be correlated to their in vivo effect on mitogen and MLC induced blast transformation, on cytotoxic effector cell function in CML and on allograft prolongation in an effort to delineate the mechanism of immunosuppressive action of anti-human thymocyte globulin and to establish valid in vitro correlates of immunosuppressive activity. BIBLIOGRAPHIC REFERENCES: Thomas, F., Thomas, J., Lee, H.M., et.al.: Studies of thymus-derived (T) Lymphocytes and marrow-derived (B) lymphocytes in renal transplant patients. Amer. Surg., 41:738, 1975. Thomas, J., Thomas, F., Wolf, J.S. and Levinson, H., et.al.: Antithymocyte globulin of high immunosuppressive potency for clinical use. Transpl. Proceed., VII:789, 1975.